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DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.
Hannon, Eilis; Dempster, Emma L; Mansell, Georgina; Burrage, Joe; Bass, Nick; Bohlken, Marc M; Corvin, Aiden; Curtis, Charles J; Dempster, David; Di Forti, Marta; Dinan, Timothy G; Donohoe, Gary; Gaughran, Fiona; Gill, Michael; Gillespie, Amy; Gunasinghe, Cerisse; Hulshoff, Hilleke E; Hultman, Christina M; Johansson, Viktoria; Kahn, René S; Kaprio, Jaakko; Kenis, Gunter; Kowalec, Kaarina; MacCabe, James; McDonald, Colm; McQuillin, Andrew; Morris, Derek W; Murphy, Kieran C; Mustard, Colette J; Nenadic, Igor; O'Donovan, Michael C; Quattrone, Diego; Richards, Alexander L; Rutten, Bart Pf; St Clair, David; Therman, Sebastian; Toulopoulou, Timothea; Van Os, Jim; Waddington, John L; Sullivan, Patrick; Vassos, Evangelos; Breen, Gerome; Collier, David Andrew; Murray, Robin M; Schalkwyk, Leonard S; Mill, Jonathan.
Affiliation
  • Hannon E; University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom.
  • Dempster EL; University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom.
  • Mansell G; University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom.
  • Burrage J; University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, United Kingdom.
  • Bass N; Division of Psychiatry, University College London, London, United Kingdom.
  • Bohlken MM; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Heidelberglaan, Utrecht, Netherlands.
  • Corvin A; Department of Psychiatry and Neuropsychiatric Genetics Research Group, Trinity Translational Medicine Institute, Trinity College Dublin, St. James Hospital, Dublin, Ireland.
  • Curtis CJ; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Dempster D; NIHR BioResource Centre Maudsley, South London and Maudsley NHS Foundation Trust (SLaM), King's College London, London, United Kingdom.
  • Di Forti M; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Dinan TG; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Donohoe G; South London and Maudsley NHS Mental Health Foundation Trust, London, United Kingdom.
  • Gaughran F; National Institute for Health Research (NIHR), Mental Health Biomedical Research Centre, South London and Maudsley NHS Foundation Trust and King's College London, London, United Kingdom.
  • Gill M; APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • Gillespie A; Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
  • Gunasinghe C; Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Hulshoff HE; National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
  • Hultman CM; Department of Psychiatry and Neuropsychiatric Genetics Research Group, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
  • Johansson V; Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Kahn RS; Department of Psychiatry, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
  • Kaprio J; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Kenis G; Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands.
  • Kowalec K; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • MacCabe J; Department of Medical Epidemiology and Biostatistics Sweden, Karolinska Institutet, Stockholm, Sweden.
  • McDonald C; Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
  • McQuillin A; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
  • Morris DW; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States.
  • Murphy KC; Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
  • Mustard CJ; Department of Public Health, University of Helsinki, Helsinki, Finland.
  • Nenadic I; Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
  • O'Donovan MC; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Quattrone D; College of Pharmacy, University of Manitoba, Winnipeg, Canada.
  • Richards AL; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Rutten BP; Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Medicine, National University of Ireland Galway, Galway, Ireland.
  • St Clair D; Division of Psychiatry, University College London, London, United Kingdom.
  • Therman S; Division of Psychiatry, University College London, London, United Kingdom.
  • Toulopoulou T; Centre for Neuroimaging and Cognitive Genomics (NICOG), School of Psychology and Discipline of Biochemistry, National University of Ireland Galway, Galway, Ireland.
  • Van Os J; Department of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
  • Waddington JL; Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom.
  • Sullivan P; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • Vassos E; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, United Kingdom.
  • Breen G; South London and Maudsley NHS Mental Health Foundation Trust, London, United Kingdom.
  • Collier DA; MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • Murray RM; Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
  • Schalkwyk LS; The Institute of Medical Sciences, Univeristy of Aberdeen, Aberdeen, United Kingdom.
  • Mill J; Department of Public Health Solutions, Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland.
Elife ; 102021 02 26.
Article in En | MEDLINE | ID: mdl-33646943
We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Psychotic Disorders / DNA Methylation / Epigenome / Schizophrenia, Treatment-Resistant Type of study: Prognostic_studies / Systematic_reviews Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Elife Year: 2021 Document type: Article Affiliation country: Country of publication:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Psychotic Disorders / DNA Methylation / Epigenome / Schizophrenia, Treatment-Resistant Type of study: Prognostic_studies / Systematic_reviews Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Elife Year: 2021 Document type: Article Affiliation country: Country of publication: